Ignite Creation Date:
2024-05-05 @ 4:56 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00353158
Status:
COMPLETED
Last Update Posted:
2024-07-08
First Post:
2006-07-14
Brief Title:
A Pilot of PediatricAdult Study of Gene Expression Profiling and Clinical Characterization of Phototoxicity
Sponsor:
National Institute of Arthritis and Musculoskeletal and Skin Diseases NIAMS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot PediatricAdult Study of Gene Expression Profiling and Clinical Characterization of Phototoxicity
Status:
COMPLETED
Status Verified Date:
2024-08-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the phototoxicity a reaction to light that is like exaggerated sunburn which occurs in people who take medications such as voriconazole a medication used to fight fungus Sunscreens might protect the skin from the reaction Although phototoxicity from voriconazole is not completely understood it may be related to how that medication is metabolized in the liver by enzymes called cytochrome P450 enzymes-and mainly by one known as 2C19 A way to evaluate phototoxicity is through microarrays which measure how much each gene is expressed in cells from tissues such as skin
Patients ages 8 and older who are scheduled to begin taking or who currently take voriconazole may be eligible for this study Also patients ages 18 to 45 in good health who have skin tone known as Type 2 which usually burns and tans only slightly following sun exposure may be eligible All patients will visit the Dermatology Clinic They will complete two questionnaires on medical history and medications as well as the skin response to sunlight and donate about 3 teaspoons of blood Patients who are scheduled to take voriconazole will visit the clinic four times that is two visits 2 consecutive days before beginning the medication and two visits on 2 consecutive days after taking it for at least 7 days Each visit will take 1 to 2 hours Patients about to take voriconazole will have a blood test and undergo a physical exam of the skin test site on the buttocks Researchers will take photographs of the specific site and do tests to measure skin reaction to ultraviolet UV light UV light will be shined on 15 small areas of the skin each 1 x 1 centimeters After 24 hours any redness that occurs on the skin will be checked Afterward patients will begin taking voriconazole according to directions by the researchers At 10 or more days later patients will visit the clinic Sunscreen will be applied and 1 hour later after administration of voriconazole a blood sample will be drawn to check the level of medication Then UV light will be shined on 23 areas of skin 1 x 1 centimeters More photographs will be taken of test sites to record changes in skin redness On the next day the skin response will be evaluated Participants in the control group will be asked to avoid UV radiation by wearing hats and clothing and using sunscreen They will be given the doxycycline an antibiotic and undergo procedures with UV light shined on small areas of the skin on the buttocks Control participants will have 7 study days with visits lasting from 1 to 3 hours and probably not exceeding 8 hours They will have two shave biopsies on Study Day 2 and on Study Day 7 to determine how the skin has responded to UV light exposures
Patients ages 8 and older who are scheduled to begin taking or who currently take voriconazole may be eligible for this study Also patients ages 18 to 45 in good health who have skin tone known as Type 2 which usually burns and tans only slightly following sun exposure may be eligible All patients will visit the Dermatology Clinic They will complete two questionnaires on medical history and medications as well as the skin response to sunlight and donate about 3 teaspoons of blood Patients who are scheduled to take voriconazole will visit the clinic four times that is two visits 2 consecutive days before beginning the medication and two visits on 2 consecutive days after taking it for at least 7 days Each visit will take 1 to 2 hours Patients about to take voriconazole will have a blood test and undergo a physical exam of the skin test site on the buttocks Researchers will take photographs of the specific site and do tests to measure skin reaction to ultraviolet UV light UV light will be shined on 15 small areas of the skin each 1 x 1 centimeters After 24 hours any redness that occurs on the skin will be checked Afterward patients will begin taking voriconazole according to directions by the researchers At 10 or more days later patients will visit the clinic Sunscreen will be applied and 1 hour later after administration of voriconazole a blood sample will be drawn to check the level of medication Then UV light will be shined on 23 areas of skin 1 x 1 centimeters More photographs will be taken of test sites to record changes in skin redness On the next day the skin response will be evaluated Participants in the control group will be asked to avoid UV radiation by wearing hats and clothing and using sunscreen They will be given the doxycycline an antibiotic and undergo procedures with UV light shined on small areas of the skin on the buttocks Control participants will have 7 study days with visits lasting from 1 to 3 hours and probably not exceeding 8 hours They will have two shave biopsies on Study Day 2 and on Study Day 7 to determine how the skin has responded to UV light exposures
Detailed Description:
Background
Phototoxicity is a sunburn-like response associated with certain medications and is a phenomenon which is not completely understood Although clinically similar to a typical sunburn reaction the gene expression changes in phototoxic skin reactions may differ from those in typical sunburn
Doxycycline is a relatively well-tolerated and known phototoxic antimicrobial which can be used in healthy volunteers to increase susceptibility to phototoxicity
Characterizing potential risk factors to phototoxicity secondary to voriconazole a broad-spectrum antifungal agent associated with potentially treatment-limiting phototoxicity may allow identification of subjects at risk for the adverse reaction via pharmacogenetic evaluation and medical record review
Subjects at risk of phototoxicity may benefit from application of effective sunscreens
Objectives
To determine the global gene expression profiles in skin exhibiting phototoxic reactions in healthy volunteers treated with doxycycline and compare expression profiles in skin exposed to ultraviolet UV radiation occurring in the absence of doxycycline
To investigate the effects of the doxycycline alone in the skin of phototoxic and non-phototoxic healthy volunteers
To characterize voriconazole-related phototoxicity reactions in subjects with the use of phototesting and to determine if these subjects may receive reasonable phototoxic protection from the use of sunblock
Eligibility
I II Healthy volunteers with skin phototype II
III Subjects scheduled to begin voriconazole therapy
IV Subjects on chronic voriconazole with or without a history of phototoxicity reaction
Previously treated healthy volunteers I II who were evaluated to be either phototoxic
OR non-phototoxic
Design
I For the Screening visit arm forty healthy volunteers will undergo screening with pertinent skin exam and blood work to evaluate ANAENA and liver function profile
II For the Study visit arm eligible healthy volunteers will undergo phototesting and will have skin biopsies prior to initiating a 3-day course of oral doxycycline 100 mg twice daily
After the last dose of doxycycline healthy volunteers will undergo on-treatment MED testing
In those demonstrating phototoxicity skin biopsies will be performed and submitted for processing for microarray analysis
III Thirty-five subjects scheduled to begin voriconazole will undergo CYP450 genotyping and baseline phototesting prior to initiation of voriconazole
Adult subjects will be invited to undergo optional skin biopsies pre-drug and on-drug
Repeat phototesting will be performed in subjects after at least 7 days of voriconazole to determine if voriconazole predisposes to phototoxicity
Subjects with voriconazole phototoxicity will be invited to undergo sunscreen testing
IV Seventy subjects with prior clinical history of voriconazole phototoxicity as well as known voriconazole phototoxicity non-reactors will undergo CYP450 genotyping and potential phototesting
To investigate the effects of the doxycycline alone in the skin of healthy volunteers previously categorized as phototoxic and non-phototoxic
Phototoxicity is a sunburn-like response associated with certain medications and is a phenomenon which is not completely understood Although clinically similar to a typical sunburn reaction the gene expression changes in phototoxic skin reactions may differ from those in typical sunburn
Doxycycline is a relatively well-tolerated and known phototoxic antimicrobial which can be used in healthy volunteers to increase susceptibility to phototoxicity
Characterizing potential risk factors to phototoxicity secondary to voriconazole a broad-spectrum antifungal agent associated with potentially treatment-limiting phototoxicity may allow identification of subjects at risk for the adverse reaction via pharmacogenetic evaluation and medical record review
Subjects at risk of phototoxicity may benefit from application of effective sunscreens
Objectives
To determine the global gene expression profiles in skin exhibiting phototoxic reactions in healthy volunteers treated with doxycycline and compare expression profiles in skin exposed to ultraviolet UV radiation occurring in the absence of doxycycline
To investigate the effects of the doxycycline alone in the skin of phototoxic and non-phototoxic healthy volunteers
To characterize voriconazole-related phototoxicity reactions in subjects with the use of phototesting and to determine if these subjects may receive reasonable phototoxic protection from the use of sunblock
Eligibility
I II Healthy volunteers with skin phototype II
III Subjects scheduled to begin voriconazole therapy
IV Subjects on chronic voriconazole with or without a history of phototoxicity reaction
Previously treated healthy volunteers I II who were evaluated to be either phototoxic
OR non-phototoxic
Design
I For the Screening visit arm forty healthy volunteers will undergo screening with pertinent skin exam and blood work to evaluate ANAENA and liver function profile
II For the Study visit arm eligible healthy volunteers will undergo phototesting and will have skin biopsies prior to initiating a 3-day course of oral doxycycline 100 mg twice daily
After the last dose of doxycycline healthy volunteers will undergo on-treatment MED testing
In those demonstrating phototoxicity skin biopsies will be performed and submitted for processing for microarray analysis
III Thirty-five subjects scheduled to begin voriconazole will undergo CYP450 genotyping and baseline phototesting prior to initiation of voriconazole
Adult subjects will be invited to undergo optional skin biopsies pre-drug and on-drug
Repeat phototesting will be performed in subjects after at least 7 days of voriconazole to determine if voriconazole predisposes to phototoxicity
Subjects with voriconazole phototoxicity will be invited to undergo sunscreen testing
IV Seventy subjects with prior clinical history of voriconazole phototoxicity as well as known voriconazole phototoxicity non-reactors will undergo CYP450 genotyping and potential phototesting
To investigate the effects of the doxycycline alone in the skin of healthy volunteers previously categorized as phototoxic and non-phototoxic
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-AR-0198 | None | None | None |